Breast Cancer
Breast cancer is a malignant tumour arising from the cells of the breast — most commonly from the cells lining the milk ducts (ductal carcinoma) or the lobules (lobular carcinoma) of the breast gland. It is the most commonly diagnosed cancer in women worldwide — accounting for approximately 2.3 million new cases and 685,000 deaths globally every year — and the leading cause of cancer death in women globally. Breast cancer is not a single disease — it is a diverse and biologically complex group of malignancies with multiple subtypes, distinct molecular profiles, different clinical behaviours and a wide range of treatment approaches. It affects women of all ages, races, nationalities and socioeconomic backgrounds — and also occurs, less commonly, in men. In India, breast cancer is the most commonly diagnosed cancer in women — with approximately 200,000 new cases diagnosed every year — and a particular concern because Indian women tend to be diagnosed at a younger age and at a more advanced stage than women in Western countries.
Overview
Breast cancer arises when cells in the breast acquire mutations — changes in their DNA — that cause them to grow and divide uncontrollably, forming a mass of abnormal tissue called a tumour. Over time, breast cancer cells can invade the surrounding breast tissue, spread to the lymph nodes under the arm (axillary lymph nodes) and ultimately spread to distant organs — a process called metastasis — most commonly to the bones, lungs, liver and brain.
The biology of breast cancer is extraordinarily diverse — even two tumours that look identical under the microscope can have completely different molecular profiles, respond differently to the same treatment and have very different prognoses. This diversity — driven by the extraordinary variety of genetic mutations, epigenetic changes and molecular alterations that can drive breast cancer development — makes breast cancer one of the most complex and scientifically fascinating cancers to study and treat.
Types of Breast Cancer
Breast cancer is classified in several ways — by the type of cell from which it arises, by its stage and by its molecular subtype:
By Cell of Origin
Invasive Ductal Carcinoma (IDC)
Invasive ductal carcinoma is the most common type of breast cancer — accounting for approximately 70–80% of all breast cancer diagnoses. It arises from the cells lining the milk ducts of the breast and has invaded through the duct wall into the surrounding breast tissue. It can spread to the lymph nodes and distant organs.
Ductal Carcinoma In Situ (DCIS)
Ductal carcinoma in situ is a non-invasive (pre-invasive) breast cancer — in which abnormal cells are confined within the milk ducts and have not yet broken through the duct wall into the surrounding tissue. DCIS is considered a precursor to invasive breast cancer — and is treated to prevent progression.
Invasive Lobular Carcinoma (ILC)
Invasive lobular carcinoma arises from the lobules (milk-producing glands) of the breast — accounting for approximately 10–15% of invasive breast cancers. ILC has a distinctive pattern of spread — infiltrating the breast tissue in single-file rows of cells — and is more difficult to detect on mammography than IDC.
Inflammatory Breast Cancer (IBC)
Inflammatory breast cancer is a rare but aggressive form of breast cancer — characterised by redness, swelling and warmth of the breast caused by cancer cells blocking the lymph vessels in the skin. IBC progresses rapidly and has a poorer prognosis than non-inflammatory breast cancers — but responds well to chemotherapy-based treatment.
Paget's Disease of the Nipple
A rare form of breast cancer involving the skin of the nipple and areola — usually associated with underlying DCIS or invasive carcinoma.
Phyllodes Tumours
Rare fibroepithelial tumours of the breast — usually benign but occasionally malignant — arising from the connective tissue stroma of the breast.
By Molecular Subtype
The molecular classification of breast cancer — based on the expression of hormone receptors and the HER2 protein — is the most clinically important classification system — as it determines treatment approach and prognosis:
Luminal A
- Oestrogen receptor (ER) positive and/or progesterone receptor (PR) positive
- HER2 negative
- Low Ki-67 (low proliferation rate)
- The most common and most favourable breast cancer subtype — generally slow-growing, responds well to hormone therapy and has an excellent prognosis
Luminal B
- ER positive and/or PR positive
- Either HER2 positive or HER2 negative with high Ki-67
- More aggressive than Luminal A — with a higher proliferation rate and less favourable prognosis — may require chemotherapy in addition to hormone therapy
HER2-Enriched
- HER2 overexpressed or amplified
- ER negative and PR negative
- Historically aggressive — but dramatically improved outcomes with targeted anti-HER2 therapies such as trastuzumab (Herceptin), pertuzumab and T-DM1
Triple-Negative Breast Cancer (TNBC)
- ER negative, PR negative and HER2 negative
- Accounting for approximately 15–20% of breast cancers — but disproportionately more common in younger women, women of African descent and women with BRCA1 mutations
- The most aggressive breast cancer subtype — with the poorest prognosis and the fewest targeted treatment options
- Chemotherapy is the mainstay of systemic treatment — though immunotherapy and PARP inhibitors have recently expanded the treatment options for selected TNBC patients
Postpartum Breast Cancer
Postpartum breast cancer — breast cancer arising during pregnancy or within the first few years following childbirth — is one of the most biologically aggressive and scientifically important subtypes of breast cancer. It is disproportionately likely to be triple-negative, to present at an advanced stage and to have a poorer prognosis than breast cancers in non-postpartum women of similar age.
The unique biology of postpartum breast cancer — shaped by the dramatic changes occurring in the breast during postpartum involution — is an active area of research at institutions including the University of Colorado Anschutz Medical Campus, where researchers including Dr. Nishant Kumar Rana are investigating the role of molecules such as SEMA7A in enabling tumour cells to adapt and survive during the postpartum period.
Risk Factors
Non-Modifiable Risk Factors
- Female sex — Breast cancer is approximately 100 times more common in women than in men
- Age — Risk increases steadily with age — the majority of breast cancers are diagnosed in women over 50
- Family history — A first-degree relative with breast cancer approximately doubles the risk
- Genetic mutations — BRCA1 and BRCA2 mutations confer a lifetime breast cancer risk of 50–85%
- Dense breast tissue — Associated with both increased cancer risk and reduced mammographic sensitivity
- Previous breast cancer or DCIS — Significantly elevated risk of contralateral breast cancer
- Exposure to ionising radiation — Particularly radiation to the chest in childhood or early adulthood
Modifiable Risk Factors
- Hormone replacement therapy (HRT) — Particularly combined oestrogen-progestogen HRT — associated with increased risk
- Oral contraceptive use — Small increase in risk
- Alcohol consumption — Dose-dependent increase in risk
- Obesity and overweight — Particularly in postmenopausal women — associated with increased risk through elevated circulating oestrogen levels
- Physical inactivity
- Late first pregnancy or nulliparity — Women who have their first child after age 30, or who never have children, have a higher risk than women who have children early
- Short duration of breastfeeding
Protective Factors
- Breastfeeding — Extended breastfeeding is associated with reduced breast cancer risk
- Physical exercise — Associated with reduced risk
- Maintaining healthy weight
- Limiting alcohol
Symptoms
Early breast cancer may be completely asymptomatic — detected only on screening mammography. Symptoms that may indicate breast cancer include:
- A new lump or thickening in the breast or armpit
- Change in breast size or shape
- Skin changes — dimpling, puckering or thickening of the skin (peau d'orange — orange peel appearance)
- Nipple changes — inversion, discharge (particularly bloody), crusting or scaling
- Redness or rash on the skin of the breast
- Persistent breast pain (less commonly associated with cancer)
- Swollen lymph nodes under the arm or around the collarbone
Any persistent or unexplained breast symptom should be promptly evaluated by a healthcare professional.
Diagnosis
Imaging
- Mammography — The primary breast cancer screening and diagnostic imaging tool — using low-dose X-rays to image the breast tissue. Screening mammography in women aged 40–74 has been shown to reduce breast cancer mortality by approximately 20–40%
- Ultrasound — Used to characterise breast lumps — distinguishing solid from cystic lesions — and to guide biopsies. Particularly useful in younger women with dense breast tissue
- MRI — The most sensitive imaging modality for breast cancer — used in high-risk screening, pre-operative staging and assessing response to neoadjuvant chemotherapy
Biopsy
Biopsy — the removal and pathological examination of tissue from a breast lesion — is the definitive method for diagnosing breast cancer. Types include:
- Core needle biopsy — The standard approach — using a hollow needle to remove cores of tissue for histological examination
- Fine needle aspiration cytology (FNAC) — Aspirating cells from a lesion using a fine needle — for cytological examination
- Vacuum-assisted biopsy — For calcifications and small lesions detected on mammography
- Excision biopsy — Surgical removal of the entire lesion — for lesions that cannot be safely sampled by less invasive means
Molecular Testing
Following diagnosis, molecular testing is performed to determine the cancer's molecular subtype and guide treatment decisions:
- ER, PR and HER2 status — By immunohistochemistry (IHC) and in situ hybridisation (ISH)
- Ki-67 — A marker of proliferation
- Gene expression profiling — Tests such as Oncotype DX, MammaPrint and Prosigna — predicting the risk of distant recurrence and the benefit of chemotherapy in hormone receptor-positive, HER2-negative early breast cancer
Treatment
The treatment of breast cancer is multidisciplinary — involving surgery, radiation therapy, chemotherapy, targeted therapy, hormone therapy and immunotherapy — tailored to the individual patient's tumour characteristics, stage and overall health:
Surgery
- Breast-conserving surgery (lumpectomy) — Removal of the tumour with a margin of normal tissue — followed by radiation therapy — the preferred surgical approach for most early breast cancers
- Mastectomy — Removal of the entire breast — indicated for larger tumours, multiple tumours, inflammatory breast cancer and patient preference
- Sentinel lymph node biopsy — Minimally invasive assessment of the axillary lymph nodes — replacing routine axillary lymph node dissection for most early breast cancers
- Axillary lymph node dissection — For patients with sentinel lymph node involvement
Radiation Therapy
Radiation therapy is standard following breast-conserving surgery — reducing the risk of local recurrence. It is also used after mastectomy in selected high-risk patients.
Systemic Therapy
Chemotherapy
Chemotherapy regimens for breast cancer typically include anthracyclines (doxorubicin, epirubicin) and taxanes (paclitaxel, docetaxel) — often in combination. Chemotherapy may be given before surgery (neoadjuvant) to shrink the tumour, after surgery (adjuvant) to reduce recurrence risk, or for metastatic disease.
Hormone Therapy
For hormone receptor-positive breast cancer:
- Tamoxifen — A selective oestrogen receptor modulator (SERM) — the standard hormone therapy for premenopausal women — taken for 5–10 years
- Aromatase inhibitors (anastrozole, letrozole, exemestane) — The preferred hormone therapy for postmenopausal women
- Ovarian suppression — Combined with tamoxifen or aromatase inhibitors in high-risk premenopausal women
- Fulvestrant — A selective oestrogen receptor degrader (SERD) — for advanced hormone receptor-positive disease
Targeted Therapy
- Anti-HER2 therapy — Trastuzumab (Herceptin), pertuzumab, T-DM1 and tucatinib — for HER2-positive breast cancer — have transformed outcomes for this subtype
- CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) — For hormone receptor-positive, HER2-negative advanced breast cancer — in combination with hormone therapy
- PARP inhibitors (olaparib, talazoparib) — For BRCA-mutated breast cancer
- PI3K inhibitors (alpelisib) — For PIK3CA-mutated hormone receptor-positive advanced breast cancer
Immunotherapy
- Pembrolizumab (Keytruda) — An immune checkpoint inhibitor approved for triple-negative breast cancer — in combination with chemotherapy for early and advanced TNBC
Breast Cancer in India
Breast cancer is the most commonly diagnosed cancer in Indian women — accounting for approximately 27% of all cancers in women in India. The epidemiology of breast cancer in India has several distinct features compared to Western countries:
- Younger age at diagnosis — Indian women tend to be diagnosed approximately 10 years younger than Western women — with a peak incidence in the 40–50 age group rather than 60–70
- More advanced stage at diagnosis — Due to lower rates of breast cancer awareness, screening and early detection
- Higher proportion of premenopausal breast cancer — Reflecting the younger age distribution
- Higher proportion of triple-negative breast cancer — Particularly in younger women
- Growing incidence — Urbanisation, changing lifestyle patterns and increased awareness are driving rising breast cancer incidence in India
Major cancer centres providing breast cancer care in India include the Tata Memorial Centre (Mumbai), AIIMS (New Delhi), Kidwai Memorial Institute of Oncology (Bengaluru) and numerous regional cancer centres across the country.
Research
Breast cancer is one of the most intensively researched cancers in the world — with major research programmes at institutions across India and internationally:
- Research on hypoxia-driven breast cancer progression — including the role of miRNA-mediated gene regulation — conducted by Indian researchers including Dr. Nishant Kumar Rana at Banaras Hindu University
- Research on postpartum breast cancer — including the role of SEMA7A — at the University of Colorado Anschutz Medical Campus
- Clinical trials of new chemotherapy regimens, targeted therapies and immunotherapy agents
- Research on genetic risk factors — including BRCA1/2 mutations — in Indian breast cancer patients
- Development of affordable, accessible screening strategies for low- and middle-income settings